Hydrogen sulfide ameliorated preeclampsia via suppression of toll-like receptor 4-activated inflammation in the rostral ventrolateral medulla of rats
Hydrogen sulfide ameliorated preeclampsia via suppression of toll-like receptor 4-activated inflammation in the rostral ventrolateral medulla of rats
复制标题
硫化氢通过抑制大鼠头端腹外侧延髓中 Toll 样受体 4 激活的炎症来改善先兆子痫
DOI：
10.1016/j.biopha.2022.113018
复制
发表时间：
2022-06-01
影响因子：
7.5
通讯作者：
Wu, Yuming
中科院分区：
文献类型：
--
作者：
Du, Jiexian;Wang, Ping;Wu, Yuming
本研究旨在确定 Toll 样受体 4 (TLR4) 介导的头侧延髓腹外侧 (RVLM) 炎症是否会导致交感神经过度活跃，从而导致先兆子痫 (PE)，以及硫化氢 (H2S) 抑制 TLR4 是否会降低 PE 的严重程度。 30 名 PE 患者和 30 名怀孕对照者参与其中。通过醋酸脱氧皮质酮和生理盐水诱导大鼠PE。将NaHS（H2S供体）、脂多糖（LPS）（TLR4激动剂）和TAK-242（TLR4抑制剂）注射到侧脑室，以研究它们对RVLM中小胶质细胞介导的炎症、交感神经激活和PE症状的影响。在PE患者中，与对照组相比，血浆NE、TNF-α和白细胞介素-1β的水平较高，而H2S的水平较低。患有PE的大鼠表现出肾交感神经活动量和血浆NE水平增加，而RVLM中H2S水平降低。在 PE 大鼠的 RVLM 中观察到小胶质细胞介导的炎症。怀孕大鼠中枢输注 LPS 会诱导小胶质细胞介导的炎症、交感神经紧张和 PE 样症状，而 TAK-242 则可减轻 PE 症状。 NaHS 治疗减轻了 PE 大鼠和 LPS 治疗怀孕大鼠 RVLM 中小胶质细胞介导的炎症、交感神经张力和 PE 症状。这些结果表明，小胶质细胞激活引起的 RVLM 炎症可能通过过度活跃的交感系统促进 PE 的进展。 H2S 可以通过抑制 RVLM 炎症来减少 PE。这些结果可能为PE的治疗提供新的靶点。
This study aims to determine whether toll-like receptor 4 (TLR4)-mediated inflammation in rostral ventrolateral medulla (RVLM) causes sympathetic overactivity leading to preeclampsia (PE) and if TLR4 inhibition with hydrogen sulfide (H2S) would reduce PE severity. Thirty patients with PE and 30 pregnant controls were involved. PE in rats was induced through deoxycorticosterone acetate and normal saline. NaHS (donor of H2S), lipopolysaccharide (LPS) (TLR4 agonist), and TAK-242 (TLR4 inhibitor) were injected in lateral cerebral ventricle to investigate their effect on microglia-mediated inflammation in RVLM, sympathetic activation, and PE symptoms. In patients with PE, plasma levels of NE, TNF-alpha, and interleukin-1 beta were high compared with those of controls, whereas levels of H2S were low. Rats with PE showed an increased amount of renal sympathetic nerve activity and plasma levels of NE, with decreased H2S levels in RVLM. Microglia-mediated inflammation was observed in the RVLM of PE rats. Central infusion of LPS in pregnant rats induced microglia-mediated inflammation, sympathetic nervous tension, and PE-like symptoms, whereas TAK-242 reduced PE symptoms. NaHS treatment lessened microglia-mediated inflammation in the RVLM, sympathetic tension, and symptoms of PE both in PE rats and LPS-treating pregnant rats.These results suggest that inflammation in the RVLM caused by microglial activation might contribute to the progression of PE via an overactive sympathetic system. H2S could reduce PE via inhibiting inflammation in the RVLM. These results might provide a new target for the treatment of PE.